SPINK2 (serine protease inhibitor Kazal-type 2) is a 7 kDa protein composed of Kazal-type domains having three disulfide bonds. In the human body, this protein is expressed in the testis or the seminal vesicle and functions as a trypsin/acrosin inhibitor (Non Patent Literature 1).
In 1991, Winter et al., reported antibody screening using phage display, and this phage display had a great impact on the development of antibody drugs by providing a method for developing fully human antibodies (Non Patent Literature 2). With recent advances in protein engineering, non-antibody scaffolds have been increasingly actively developed using display techniques such as phage display or ribosome display. These non-antibody scaffolds, also called engineering binding (affinity) proteins, etc., refer to artificial proteins provided with antibody variable region (CDR)-like binding regions. The non-antibody scaffolds have binding activity against protein X to be targeted and permit protein-protein interaction. In addition, the non-antibody scaffolds have beneficial characteristics from the viewpoint of productivity, immunogenicity, tissue infiltration, etc. As typified by Kunitz domain library (Dyax Corp.) (Patent Literature 1), anticalin (Pieris AG), or the like, only limited types of non-antibody scaffolds have been developed, though their scientific or industrial rise has been desired. Thus, the development of a novel non-antibody scaffold against a disease-related molecule has been desired (Non Patent Literature 3).